Immunotherapy Drug Durvalumab Shines in Most Recent Mesothelioma Trial

Another new study confirms what Johns Hopkins researchers have been banking on – that the immunotherapy drug durvalumab can make chemotherapy more effective for mesothelioma patients. 

Durvalumab (IMFINZI) is an immune checkpoint inhibitor. It works by blocking the action of PD-1, a protein that mesothelioma cells use to protect themselves. 

Researchers theorized that deactivating PD-1 with the immunotherapy drug durvalumab might make mesothelioma tumors more responsive to chemotherapy. The latest study results, published in Nature Medicine, suggest that they were right. 

The findings could have implications for people around the world with inoperable malignant mesothelioma.

How the Immunotherapy Drug Durvalumab Helps Fight Mesothelioma

Durvalumab is one of several immune checkpoint inhibitors showing promise for mesothelioma in recent years. Keytruda (pembrolizumab) is another one. Like the immunotherapy drug durvalumab, it blocks the PD-1 protein. 

But most people diagnosed with mesothelioma do not start with immunotherapy. Chemotherapy with Alimta is the gold standard for first-line mesothelioma treatment. Surgery can also extend survival. 

Unfortunately, about 60 percent of mesothelioma patients fail to respond to chemotherapy. Many of them are not candidates for surgery either. The Johns Hopkins research suggests that the immunotherapy drug durvalumab could be a breakthrough for these patients. 

What the Research Says

For mesothelioma patients on standard chemotherapy, median overall survival is right around one year. But the Johns Hopkins study showed that adding durvalumab extended survival to more than 20 months. 

For people with epithelioid mesothelioma, the most common subtype, the news was even better. The findings show these patients had a median overall survival of 24.3 months – almost twice as long as chemotherapy alone. 

The researchers found that the more genomic anomalies a patient had, the better they tended to respond to the immunotherapy drug durvalumab. 

“Our findings indicate that concurrent durvalumab with platinum-based chemotherapy has promising clinical activity and that responses are driven by the complex genomic background of malignant pleural mesothelioma,” report the authors, Patrick Forde, Valsamo Anagnostou, and Suresh Ramalingam. 

Manageable Side Effects Move Study on to Phase 3

Researchers gave the chemotherapy-immunotherapy combination to 55 patients with unresectable pleural mesothelioma. They report that the main side effects from the treatment were ones already associated with chemotherapy. Side effects from the immunotherapy drug durvalumab were mostly mild. 

Based on the profiles of responsive patients, the researchers identified a number of tests that might help predict patient response to the chemotherapy-immunotherapy combination. 

The next step is to test the combination in a larger study. The phase 3 clinical trial aims to enroll 480 mesothelioma patients between 18 and 70. Patients must not have had any treatment yet and their cancer must not be removable surgically. 

Source:

Forde, P, et al, “Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial”, November 8, 2021, Nature Medicine, Open Access online article, https://www.nature.com/articles/s41591-021-01541-0